A novel homozygous MFN2 mutation associated with severe and atypical CMT2 phenotype

作者：Iapadre Giulia; Morana Giovanni; Van Maria Stella; Pinto Francesca; Lanteri Paola; Tessa Alessandra; Santorelli Filippo Maria; Striano Pasquale; Verrotti Alberto^*

来源：European Journal of Paediatric Neurology, 2018, 22(3): 563-567.

DOI：10.1016/j.ejpn.2017.12.020

• Charcot-Marie-Tooth
• CMT2
• Mitofusin 2
• MFN2
• Neuropathy
• Homozygous mutation

Background: Charcot-Marie-Tooth (CMT) neuropathies represent the most common forms of inherited polyneuropathies. CMT2A, the axonal form, accounts for about one third of all CMT cases. Variants in the MFN2 gene have been recognized to be a major cause of CMT2A. To date, more than 100 pathogenetic mutations in MFN2 have been identified, leading to different neurological clinical spectrum, varying from hereditary neuropathies to more severe clinical phenotypes. Pathogenic variants in MFN2 mainly act in a dominant manner, although in a few sporadic or familial cases, homozygous or compound heterozygous mutations have been reported.
Results: We describe a child carrying a novel homozygous MFN2 mutation leading to an early-onset sensorimotor axonal neuropathy with an atypical and severe phenotype.
Conclusion: The case highlights a very rare mechanism of inheritance for MFN2 mutations and expands the clinical and allelic variance of severe CMT2A phenotype. Moreover, it proposes the involvement of cerebellar peduncles observed at neuroimaging as a novel clue to suspect the diagnosis and address genetic testing.

• 出版日期2018-5